1. Field of the Invention
The invention relates to a process for manufacturing organised collagen structures, in particular of human origin, and organised collagen structures corresponding thereto.
2. Brief Description of the Prior Art
It is known that collagen is the most abundant protein in mammals. It constitutes the principal fibrous element of skin, of the bones, tendons, cartilages, blood vessels and of the teeth. It is present in smaller proportions in almost all organs; it appears in the form of organised structures linked to cellular tissue, which structures are fibers or membranes.
The basic structural unit of an organised collagen structure is the tropocollagen fibril. The tropocollagen fibrils combine either to form collagen fibers which display, among other features, striations perpendicular to their axis spaced at approximately 70 nm relative to each other as well as a very high tensile strength, or to form collagen membranes.
The collagen fibers and membranes being very important constituents of the human body, attempts have been made at the in vitro reconstitution of collagen of a kind the physical and biological chacateristics of which are to closely approximate those of the collagen in vivo.
Several processes for collagen reconstitution are known to date, all starting with an animal or human tissue. One of these processes, described in 1979 by M. CHAPIL et al. in "Medical and Surgical Applications of Collagen" (International Revue of Connective Tissue Research, Vol. 6, pp. 1-55) consists in solubilizing in an acid media a part of the collagen contained in an animal tissue, namely a bovine tendon, after an enzymatic treatmen. There is obtained in this manner a collagen suspension. The latter is then reconstituted either by dialysis or by precipitation in a saline medium. The collagen structure thus obtained is an amorphous precipitate constituted by non-fibrillary denaturated collagen.
This structure is in general not directly applicable for medical purposes. In fact, the collagenous material thus obtained lacks tensile strength in moist media and has little resistance against enzymatic degradation when applied to living tissues. Accordingly, this collagen must undergo special pre-treatments to remedy these drawbacks. Once these treatments have been completed, the collagen may have, among others, a gel-like or spongious form. It can then be used as haemostatic agent, as a wet surgical dressing or as a wet dressing for burns.
However, this denaturated or molecular collagen, although having undergone a treatment to reform the physical and biological characteristics approximating those of in vivo collagen, does not always satisfy requirements, in particular those of good mechanical properties in wet dressings, because it lacks the in vivo organised structure, notably the collagen fibers are not present in this artificial collagen. Moreover, the production of certain biological prostheses would require the use of collagen membranes owing to the mechanical properties of said membranes.
These considerations have led to a more detailed study of the fibrillogenesis of collagen. The fibers reconstituted from the skin of the rabbit have been found in a series of experiments described in 1969 by I. GOLDSTEIN (C.R. Academie des Sciences of Paris, vol. 268, pp. 2446-2448), but the yield of such fibers is very low, of the order of 0.5% (calculated on the weight of the original skin) when starting from an extract of animal skin.
Although these reconstituted fibers offer considerable advantages over the denaturated collagen gels, they remain nevertheless of non-human origin and are thus likely to be rejected by a human organ to which they are applied or into which they would be implanted.